Analytical treatment interruption (ATI) is an important tool to evaluate interventions designed to achieve HIV eradication or long-term control without antiretroviral therapy. We convened a stakeholder workshop to update the published recommendations for the conduct of ATI studies. Important changes to the recommendations include more lenient entry criteria on CD4 count, CD4 nadir, and past medical history, and allowance for greater variation based on regional standards. As the mechanism of potential HIV remission might rely on immune control, the criteria for antiretroviral therapy resumption now allow for longer periods of viraemia at higher levels to stimulate a more robust immune response. Greater emphasis is placed on the importance of psychosocial monitoring and support, the prevention of HIV transmission to partners during ATI, and the integration of sociobehavioural research into ATI studies. Recommendations for the conduct of paediatric and adolescent ATI trials, absent from previous guidelines, are now included. These recommendations, based on current available data, expert opinion, and community consultation, aim to help steer the safe and ethical implementation of the next generation of ATI trials as we continue the search for an HIV cure.

Female genital schistosomiasis (FGS) is a sequela of infection with a waterborne parasite prevalent in sub-Saharan Africa and is associated with increased HIV risk. Diagnosis of FGS involves visual colposcopic identification of lesions on the cervix or vaginal walls. Previous studies have utilized digital image processing methods with statistical validation, and more recently, an artificial intelligence (AI)-based approach has also been explored. In this work, we sought to evaluate the performance of an AI model for identifying the presence of FGS from cervical photographs. Colposcopy images were obtained from 340 subjects in Zambia. Ground truth for presence or absence of FGS was determined by trained expert human examiners using visual assessment of images. Examiners also provided a FGS severity score between 0-8 for each image based on the number of lesions and the cervical quadrants affected, where 8 denotes highest severity and 0 denotes no FGS. The images were pre-processed with specular reflection artifact removal and image cropping to focus on the regions corresponding to the cervix and the transformation zone. The preprocessed dataset was randomly divided into training (FGS = 71, no FGS = 71) and testing (FGS = 21, no FGS = 177) cohorts. Image representations in the latent space were obtained using an ensemble of pre-trained machine learning models to further classify the image into FGS and no FGS. The best performance in the testing dataset was obtained at subject-level with area under the curve (AUC) =0.70 (95% Confidence interval: 0.58 - 0.82), Specificity = 0.68, and Sensitivity = 0.71, against the ground truth. Subjects with higher FGS severity scores (between 5-8) had high prediction rate by the machine classifier compared to those with lower severity scores (between 1-4). Machine learning shows promise in detecting FGS from limited colposcopy images. Early, accurate diagnosis may enhance reproductive health, and reduce HIV transmission risks, safeguarding maternal and child health.

BACKGROUND:Even within the context of antiretroviral treatment and prevention, an HIV-1 vaccine remains the best strategy for ending the HIV/AIDS epidemic. A vaccine is particularly needed in sub-Saharan Africa, where HIV-1 greatly affects people's lives and economy. Here, we aimed to assess the safety and immunogenicity of candidate T-cell vaccines in African populations. METHODS:HIV-CORE 006 was a double-blind, randomised, placebo-controlled phase 1 trial conducted across four clinical research centres in Uganda, Kenya, and Zambia. Eligible participants were not pregnant, were living without HIV-1 or HIV-2, had a low likelihood of acquiring HIV-1, were aged 18-50 years, fully comprehended the purpose and details of this study as outlined in the participant information sheet, and passed an assessment of understanding before providing written informed consent. Participants were randomly assigned (9:2) to receive either a vaccine regimen or a placebo. The vaccine was administered as ChAdOx1.tHIVconsv1 (C1) followed by MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4) in regimen C1-M3M4. The first primary outcome was the vaccines' safety assessment, assessed in all participants who received at least one vaccine or placebo dose. The second primary outcome evaluated the C1-M3M4 regimen's induction of HIVconsvX-specific T-cell responses by assessing the proportion of vaccine recipients who responded to the vaccination, assessed in all participants who received all doses of vaccine or placebo as per protocol. This study is registered with ClinicalTrials.gov, NCT04553016, and the Pan-African Clinical Trials Registry PACTR202006495409011, and is now closed. FINDINGS:Between July 15, 2021, and Nov 2, 2022, 89 healthy adults living without HIV-1 were randomly assigned, with 88 receiving either the vaccine (n=72) or placebo (n=16). Of these 88 participants, 57 (65%) were male and 31 (35%) were female. The C1, M3, and M4 vaccine components were well tolerated and induced HIVconsvX-specific responses in 70 (99%) of the 71 participants who completed all vaccine doses. Vaccine-elicited T cells peaked at a median of 2310 (IQR 1080-4480) IFN-γ spot-forming units per 106 peripheral blood mononuclear cells and recognised a median of eight (five to ten) of ten peptide pools spanning the HIVconsvX immunogen. The total frequencies of elicited T cells decreased 4·6 times over a 40-week follow-up period compared with the peak responses. Upon antigenic re-exposure, T cells proliferated, exhibited multiple effector functions, and inhibited HIV-1 representatives from clades A, B, C, and D. INTERPRETATION:Results from key sub-Saharan African populations supported the safety of the vaccine regimen previously shown in the first-in-human trial in the UK. The induction of T cells and their characteristics encourage vaccine integration into HIV-1 cure strategies, which could inform HIV-1 prevention efforts. FUNDING:The European and Developing Countries Clinical Trials Partnership.

Sex differences play a role in the pathogenesis of a number of viral diseases. In HIV-1, several studies have reported that chronically infected women have significantly lower plasma viremia than men, although the exact mechanism by which this occurs has yet to be identified. We have performed bulk RNA-seq experiments comparing gene expression between CD4+ T cells from acutely HIV-1–infected men and women in Zambia, because we observe lower viral load (VL) despite higher CD4+ T-cell activation in these women during acute/early infection. In a univariate analysis, we have identified a number of differentially expressed genes in naïve, central memory, and effector memory CD4 T cells of women with consistent elevated expression of genes linked to type 1 interferon (IFN) signaling. Moreover, after controlling for differences in VL and CD4+ T-cell count, genes within the type I IFN signaling pathway were further shown to be more highly expressed in women, whereas those genes more highly expressed in men showed no such enrichment. A subset of the genes highly expressed in women was further identified, including several involved in type I IFN signaling in response to viral infections (IRF7, DDX58, SAMHD1, OAS2, and TRIM14), that both are more highly expressed in CD4+ T cells from women and negatively correlated with VL, suggesting that they play a role in the comparative control of VL observed in women.

OBJECTIVE:To compare HIV incidence among female sex workers (FSW) and single mothers, and to determine the factors associated with seroconversion among both populations. DESIGN:Prospective cohort conducted in Lusaka and Ndola, Zambia between 2012 and 2022. METHODS:Study staff recruited FSW from common sex work locales and recruited single mothers from postnatal infant vaccination clinics. Enrolled participants were HIV-negative, aged 18-45, and identified as either a FSW or single mother. We measured HIV incidence and assessed associated factors using Poisson regression with adjusted rate ratios (aRRs) and 95% confidence intervals (CIs). RESULTS:The study enrolled 2539 women (1533 FSW and 1006 single mothers). HIV incidence was not statistically different for FSW (3.24 per 100 person-years; 95% CI: 2.63-3.95) and single mothers (2.64 per 100 person-years; 95% CI: 2.00-3.43). Factors associated with HIV seroconversion were positive syphilis (aRR: 2.03; 95% CI: 1.46-2.83) and trichomonas (aRR: 1.48; 95% CI: 1.06-2.06) diagnoses, inconsistent condom use (aRR: 1.60; 95% CI: 1.06-2.40), and greater than 6months follow-up time in the study (aRR: 2.45; 95% CI: 1.52-3.94). CONCLUSIONS:Single mothers share similar HIV risk to FSW, and both populations require targeted interventions. For single mothers, government postnatal clinics should combine comprehensive sexual education with screening and treatment for syphilis and trichomoniasis. For FSW, we recommend integrated and accessible interventions to prevent HIV and sexually transmitted infections. Future studies should investigate the social determinants of condom use among both FSW and single mothers.

Background: Vaccine hesitancy (VH) remains a major threat to global health that can reverse the progress in tackling vaccine-preventable diseases. Vaccine uptake among adolescent Girls and young women (AGYW) is often low. We assessed VH using a validated scale among AGYW in Uganda, Zambia, and South Africa. Methods: From June 2023 to February 2024, we recruited AGYW from fishing communities in Uganda, urban and peri-urban locations in Lusaka and Ndola, Zambia, and mining communities in Rustenburg, South Africa. Eligible participants were aged 15–24 years, sexually active, and HIV-negative but at risk for HIV acquisition. We collected demographic, HIV-related behavioral data, and vaccine hesitancy data using a structured questionnaire. Vaccine confidence was assessed using the 10-question Vaccine Hesitancy Scale that describes two factors, i.e., “vaccine confidence” and “risk tolerance”. Exploratory and Confirmatory Factor Analyses were performed to assess scale validity and internal consistency. Logistic regression was used to determine associations between demographics and vaccine confidence. Results: A total of 1213 AGYW participated in the study, with a mean age of 19.4 (SD ± 2.6) years. More than half (54%) were aged between 15 and 19 years. The majority of AGYW (94%) strongly believed that vaccines were important for their health and the community and that vaccination is a good way to protect them from diseases. About two-thirds of the AGYW (66%) indicated that they were concerned about the adverse effects of vaccines, while 30% responded that they did not need vaccines for diseases that were not common. We observed that 951 (78%) of the AGYW reported high vaccine confidence, while 494 (41%) reported low concerns over risks. Vaccine confidence varied across countries, with Zambia and Uganda showing lower vaccine confidence (adjusted odds ratios of 0.28 and 0.45, respectively, p < 0.005) in comparison to South Africa. Conclusions: A high level of vaccine confidence was observed among AGYW. Vaccine confidence among AGYW was driven more by the trust in vaccine safety and the need to protect communities against diseases. These findings suggest the potential for acceptance of vaccines, including future HIV vaccines, among AGYW. Despite high levels of vaccine confidence, concerns over vaccine risks remain substantial and must be addressed.

People with HIV (PWH) are understudied in COVID-19 vaccine trials, leaving knowledge gaps on whether the identified immune correlates of protection also hold in PWH. CoVPN 3008 (NCT05168813) enrolled predominantly PWH and reported lower COVID-19 incidence for a Hybrid vs. Vaccine Group (baseline SARS-CoV-2-positive and one mRNA-1273 dose vs. negative and two doses). Using case-cohort sampling, antibody markers at enrolment (M0) and four weeks post-final vaccination (Peak) are assessed as immune correlates of COVID-19. For the Hybrid Group [n = 287 (195 PWH)], all M0 markers inversely correlate with COVID-19 through 230 days post-Peak, with 50% inhibitory dilution BA.4/5 neutralizing antibody titer (nAb-ID50 BA.4/5) the strongest and only independent correlate (HR per 10-fold increase=0.46, 95% CI 0.28, 0.75; P = 0.002). For the Vaccine Group [n = 115 (86 PWH)], Peak nAb-ID50 BA.4/5 correlates with reduced COVID-19 risk (1.9%, 1.1%, and 0.3% at titers 10, 100, and 1000 AU/ml) through 92, but not 165, days post-Peak. Using multivariable Cox analysis of binding and nAb, nAb titers predict COVID-19 in PWH. Two doses of a 100-µg Ancestral strain mRNA vaccine in baseline-SARS-CoV-2-negative individuals elicit sufficient cross-reacting Omicron antibodies to reduce COVID-19 incidence for 90 days post-Peak, but viral evolution and waning antibodies abrogate this protection thereafter.

A better understanding of the immune responses associated with future viral control in humans during acute HIV-1 infection (AHI) is critical to inform vaccines and immune-based therapeutics. Natural killer (NK) cells and CD8 + T-cells are pivotal in antiviral defence, yet the dynamics and complementary roles of these effector subsets during AHI with different HIV-1 subtypes remain poorly understood. Access to a unique patient cohort recruited during and post-peak HIV-1 viral load with different HIV-1 subtypes and followed up longitudinally in the absence of antiretroviral therapy up to six years post estimated date of infection (EDI) provided a rare opportunity to fill this knowledge gap. Our data show an early expansion of FcεRγ - CD57 + NK cells with classical adaptive traits concomitant with an enhanced capacity for antibody-dependent cellular cytotoxicity (ADCC) and reactivity against HIV-1 antigens. This distinctive NK cell profile was more abundant in donors with subtype A infection compared to non-subtype A, partially driven by elevated pro-inflammatory cytokine levels and changes in the epigenetic landscape. The accumulation of adaptive NK cells during the first month of infection contributed to the optimal activation of CD8 + T-cells, promoting virus-specific responses. Notably, individuals with higher levels of FcεRγ - CD57 + adaptive NK cells during the first month of infection were more likely to exhibit long-term viral control in the absence of ART. These findings underscore the critical role of early, high-magnitude adaptive NK cell responses in CD8 + T-cell activation and subsequent immune control. This work provides novel insights into the correlates of protective immunity against HIV-1 infection, with implications for preventative or therapeutic vaccine strategies aimed at promoting adaptive NK cell responses. One Sentence Summary:Early expansion of adaptive NK cells during acute HIV-1 infection promotes long-term viral control.

Background:With limited access to mRNA COVID-19 vaccines in lower income countries, and people living with HIV (PLWH) largely excluded from clinical trials, Part A of the multicentre CoVPN 3008 (Ubuntu) study aimed to assess the safety of mRNA-1273, the relative effectiveness of hybrid versus vaccine immunity, and SARS-CoV-2 viral persistence among PLWH in East and Southern Africa during the omicron outbreak. Methods:Previously unvaccinated adults with HIV and/or other comorbidities associated with severe COVID-19 received either one (hybrid immunity) or two (vaccine immunity) 100-mcg doses of ancestral strain mRNA-1273 in the first month, depending on baseline evidence of prior SARS-CoV-2 infection. In a prospective cohort study design, we used covariate-adjusted Cox regression and counterfactual cumulative incidence methods to determine the hazard ratio and relative risk of COVID-19 and severe COVID-19 with hybrid versus vaccine immunity within six months. The ongoing Ubuntu study is registered on ClinicalTrials.gov (NCT05168813) and this work was conducted from December 2021 to March 2023. Findings:Between December 2021 and September 2022, 14,237 participants enrolled, and 14,002 (83% PLWH, 69% SARS-CoV-2 seropositive) were included in the analyses. Vaccinations were safe and well tolerated. Common adverse events were pain or tenderness at the injection site (26.7%), headache (20.4%), and malaise (20.3%). Severe adverse events were rare (0.8% of participants after the first and 1.1% after the second vaccination), and none were life-threatening or fatal. Among PLWH, the median CD4 count was 635 cells/μl and 18.5% had HIV viraemia. The six-month cumulative incidences in the hybrid immunity and vaccine immunity groups were 2.02% (95% confidence interval [CI] 1.61-2.44) and 3.40% (95% CI 2.30-4.49) for COVID-19, and 0.048% (95% CI 0.00-0.10) and 0.32% (95% CI 0.59-0.63) for severe COVID-19. Among all PLWH the hybrid immunity group had a 42% lower hazard rate of COVID-19 (hazard ratio [HR] 0.58; 95% CI 0.44-0.77; p < 0.001) and a 73% lower hazard rate of severe COVID-19 (HR 0.27; 95% CI 0.07-1.04; p = 0.056) than the vaccine immunity group, but this effect was not seen among PLWH with CD4 counts <350 cells/μl or HIV viraemia. Twenty PLWH had persistent SARS-CoV-2 virus at least 50 days. Interpretation:Hybrid immunity was associated with superior protection from COVID-19 compared to vaccine immunity with the ancestral mRNA-1273 vaccine. Persistent infections among immunocompromised PLWH may provide reservoirs for emerging variants. Funding:National Institute of Allergy and Infectious Diseases.

IntroductionHIV-1 subtype A and subtype C infections have different rates of clinical disease progression, with subtype C infected individuals in the IAVI Protocol C multisite acute infection cohort having a 60% faster CD4 loss compared to subtype A.MethodsIn order to investigate whether differences were due to the phenotype of the transmitted founder virus (TFV), or inflammatory cytokines and chemokines, known to drive pathogenesis, we PCR amplified, sequenced and constructed infectious molecular HIV-1 clones from the plasma of 30 acutely infected individuals in Rwanda and Zambia. We next compared the inflammatory plasma cytokine/chemokine profiles of individuals pre- and post-the estimated date of infection of 20 Rwandan individuals infected with subtype A and 34 Zambians infected with subtype C HIV-1.ResultsA comparison of the replicative capacity of 14 subtype A and 16 subtype C TFV showed that they had similar replicative capacity (RC) scores. Nevertheless, high TFV RC scores were linked to more rapid CD4+ T cell loss, and higher inflammatory cytokine levels irrespective of subtype. Multivariable analyses showed that individuals infected with subtype C exhibited a significant increase in the levels of eleven pro-inflammatory cytokines/chemokines after infection, while, in subtype A infections only six cytokines were significantly elevated postinfection. Despite these differences, at 3-months post infection, similar overall biomarker profiles were observed in individuals infected with subtype A or subtype C viruses, primarily due to higher pre-infection baseline biomarker levels in Rwanda. In the combined cohort, we found a highly significant association between faster CD4+ T cell decline and higher levels of ITAC (CXCL11), which in turn was linked to higher TFV RC.DiscussionOverall, the data presented here argue against TFV RC as the basis for different pathogenic outcomes in the subtypes A and C. Moreover, levels of inflammatory cytokines that might drive disease progression were similar during acute infection indicating that additional studies are required to understand the mechanism underlying differences in disease progression between the two subtypes. For both subtypes, high levels of ITAC during acute HIV-1 infection are linked to rapid disease progression.

Background:Human immunodeficiency virus type 1 (HIV-1) is one of the fastest-evolving human pathogens. Understanding HIV-1 transmission, within-host adaptation, and evolutionary dynamics is pivotal for development of interventions and vaccines. HIV-1 infection is generally caused by a single transmitted founder virus (TFV), and TFV sequences are typically obtained using single genome amplification (SGA). However, suboptimal sample quality can cause sequencing failures, representing considerable losses considering the scarcity of acute HIV-1 infection (AHI) samples. Sequencing failures may be mitigated by molecular cloning (MC), which can be less vulnerable to sample quality but more susceptible to polymerase chain reaction (PCR) errors. Here, we explore the feasibility of supplementing SGA with MC data using samples from clinical and research cohorts to determine whether sequence diversity and evolutionary rate estimates are comparable between the techniques. Methods:Plasma samples were selected from participants with documented AHI from an East African research cohort (the International AIDS Vaccine Initiative, 2006-2011) and a clinical cohort from Sweden (1983-2011). SGA and MC sequencing were done on the HIV-1 env V1-V3 region (~940 base pairs). Within-host sequence diversity was determined from maximum likelihood phylogenetic trees, and evolutionary rate by Bayesian phylogenetic analysis. Highlighter plots, Hamming distances, and assessment of star phylogenies were used to quantify TFVs. Results:One hundred participants (median age 30.3 years, 15% female), contributing 350 samples from four longitudinal time points, 10-540 days post-infection, met the inclusion criteria. SGA succeeded on 90% of research cohort and 48% of clinical cohort samples. Comparative analysis of linked SGA and MC data from 10 samples indicated that approximately eight sequences were necessary for diversity estimates. Consistently higher sequence diversity was observed among MC relative to SGA sequences (median [IQR]: 0.009 [0.003, 0.015] and 0.004 [0.001, 0.012] substitutions/site, P = .002), whereas evolutionary rates were comparable between the two methods (0.016 [0.012, 0.019] and 0.011 [0.008, 0.020] substitutions/site/year, P = .232). Five participants with samples obtained within 45 days post-infection were eligible for TFV quantification, and all found to have one TFV using both techniques. Conclusion:MC data is a suitable supplement for SGA-based HIV-1 studies to preserve the value of precious samples for analysis of evolutionary rate, but not for sequence diversity.

New vaccines, technologies, and regulations, alongside increased demand for vaccines, all require prioritization and coordination from key players within the vaccine sector. Inter-agency Coordinating Committees (ICC) support decision-making and coordination at the national-level and act as key drivers for sustainable improvements in vaccination programming. We utilized a previous qualitative case study, which investigated critical success factors for high routine immunization coverage in Zambia from 2000-2018, specifically to study the Zambian ICC. Qualitative data were collected between October 2019 and February 2020, including key informant interviews (n = 66) at the national, provincial, district, and health facility levels. Thematic analysis was applied to understand the role of the Zambian ICC and its impact on the policy environment over time. Within our study period, the ICC demonstrated the following improvements: 1) expanded membership to include diverse representation; 2) expanded scope and mandate to include maternal and child health in decision-making; and 3) distinct roles for collaboration with the Zambia Immunization Technical Advisory Group (ZITAG). The diverse and expansive membership of the Zambian ICC, along with its ability to foster government commitment and lobby for additional resources, supported improvements in immunization programming. The Zambian ICC holds considerable influence on government agencies and external partners, which facilitates procurement of funding, policy decisions, and strategic planning.

Objectives Community health workers are essential to front-line health outreach throughout low-income and middle-income countries, including programming for early childhood immunisation. Understanding how community health workers are engaged for successful early childhood vaccination among countries who showed success in immunisation coverage would support evidence-based policy guidance across contexts.Design We employed a multiple case study design using qualitative research methods.Setting We conducted research in Nepal, Senegal and Zambia.Participants We conducted 207 interviews and 71 focus group discussions with 678 participants at the national, regional, district, health facility and community levels of the health systems of Nepal, Senegal and Zambia, from October 2019 to April 2021. We used thematic analysis to investigate contributing factors of community health worker programming that supported early childhood immunisation within each country and across contexts.Results Implementation of vaccination programming relied principally on the (1) organisation, (2) motivation and (3) trust of community health workers. Organisation was accomplished by expanding cadres of community health workers to carry out their roles and responsibilities related to vaccination. Motivation was supported by intrinsic and extrinsic incentives. Trust was expressed by communities due to community health worker respect and value placed on their work.Conclusion Improvements in immunisation coverage was facilitated by community health worker organisation, motivation and trust. With the continued projection of health worker shortages, especially in low-income countries, community health workers bridged the equity gap in access to vaccination services by enabling wider reach to underserved populations. Although improvements in vaccination programming were seen in all three countries—including government commitment to addressing human resource deficits, training and remuneration; workload, inconsistency in compensation, training duration and scope, and supervision remain major challenges to immunisation programming. Health decision-makers should consider organisation, motivation and trust of community health workers to improve the implementation of immunisation programming.

BackgroundThe World Health Organization estimates that 56 million women and girls live with female genital schistosomiasis (FGS) in sub-Saharan Africa. FGS is often confused with symptoms of other genital abnormalities, and gold standard diagnosis with colposcopy is infeasible in most health facilities. Schistosomiasis haematobium is endemic in Zambia, yet routine screening or diagnostic efforts for FGS remain unavailable. Our study aimed to develop and pilot test a feasible FGS screening algorithm to implement in Zambian government clinics.Methodology/Principal FindingsWe recruited 499 women from a longitudinal cohort of HIV-negative adult women in Lusaka and Ndola, Zambia. We used demographic, risk factor, and symptom data collected from standardized surveys, gynecological exams, and laboratory tests to develop a screening algorithm for FGS among a derivation cohort (n=349). After cross-validation using 5-fold iterative resampling, the algorithm was applied in a holdout sample of the cohort (n=150). The prevalence of FGS (ascertained by expert review) was 23.4% in the study population. The screening algorithm included childhood and travel exposure to rivers and streams; testing positive for visual inspection of the cervix with acetic acid; hematuria; reporting less than the median average age at sexual debut (<17 years); when asked what diseases can be transmitted via freshwater exposure, reporting ‘none’; being born outside of Lusaka or Copperbelt Province; and reporting occupation as ‘Housekeeper’. The screening algorithm had reasonable discrimination in the derivation cohort (area under the curve [AUC]=0.69, 95% confidence interval [CI]: 0.66-0.79, p-value<0.001). Using a score cut off ≥ 2 the risk algorithm in the derivation cohort had 77% sensitivity, 48% specificity, 35% positive predictive value, and 85% negative predictive value.Conclusions/SignificanceGiven the prevalence of FGS and associated morbidities, improved screening for FGS is imperative. We developed a simple screening algorithm to improve the diagnosis and treatment of FGS among adult women in Zambian government clinics.

Voluntary medical male circumcision (VMMC) is a recommended HIV prevention strategy that few studies have promoted to HIV-negative men in serodiscordant relationships. We conducted a cross-sectional study on uptake and perceptions of VMMC among serodiscordant couples between 2012 and 2015. Heterosexual couples attending couples voluntary counselling and testing for HIV who had discordant results (M-, F+) were referred for VMMC. At least one month after counselling and referral, 343 men were surveyed on uptake and perceptions of VMMC. A subset of 134 uncircumcised men responded to another survey assessing their intention to uptake VMMC and reasons for not getting circumcised. Forty percent (n = 62) of men eligible for VMMC either up took (n = 22) or planned to uptake circumcision (n = 40). The most cited reasons for not getting circumcised were the inability to get time off work (34%) and culture/traditions (26%). These findings support integrated approaches, pairing evidence-based HIV prevention interventions such as couples voluntary counselling and testing with VMMC, and targeting men at highest risk for HIV. Additional counselling may be needed for couples whose cultural backgrounds do not support VMMC.

We evaluated changes in female genital schistosomiasis (FGS) 6 to 12 months after praziquantel treatment among 43 adult Zambian women. Most women (60%) experienced decreased FGS severity and 23% experienced complete lesion resolution. This is the first study to demonstrate a meaningful effect of praziquantel treatment of FGS in adult women.

The complex dynamics of protein expression in plasma during hyperacute HIV-1 infection and its relation to acute retroviral syndrome, viral control, and disease progression are largely unknown. Here, we quantify 1293 blood plasma proteins from 157 longitudinally linked plasma samples collected before, during, and after hyperacute HIV-1 infection of 54 participants from four sub-Saharan African countries. Six distinct longitudinal expression profiles are identified, of which four demonstrate a consistent decrease in protein levels following HIV-1 infection. Proteins involved in inflammatory responses, immune regulation, and cell motility are significantly altered during the transition from pre-infection to one month post-infection. Specifically, decreased ZYX and SCGB1A1 levels, and increased LILRA3 levels are associated with increased risk of acute retroviral syndrome; increased NAPA and RAN levels, and decreased ITIH4 levels with viral control; and increased HPN, PRKCB, and ITGB3 levels with increased risk of disease progression. Overall, this study provides insight into early host responses in hyperacute HIV-1 infection, and present potential biomarkers and mechanisms linked to HIV-1 disease progression and viral load.

BackgroundUnderstanding how HIV affects SARS-CoV-2 immunity is crucial for managing COVID-19 in sub-Saharan populations due to frequent coinfections. Our previous research showed that unsuppressed HIV is associated with weaker immune responses to SARS-CoV-2, but the underlying mechanisms are unclear. We investigated how pre-existing T cell immunity against an endemic human coronavirus HCoV-NL63 impacts SARS-CoV-2 T cell responses in people living with HIV (PLWH) compared to uninfected individuals, and how HIV-related T cell dysfunction influences responses to SARS-CoV-2 variants.MethodsWe used flow cytometry to measure T cell responses following PBMC stimulation with peptide pools representing beta, delta, wild-type, and HCoV-NL63 spike proteins. Luminex bead assay was used to measure circulating plasma chemokine and cytokine levels. ELISA and MSD V-PLEX COVID-19 Serology and ACE2 Neutralization assays were used to measure humoral responses.ResultsRegardless of HIV status, we found a strong positive correlation between responses to HCoV-NL63 and SARS-CoV-2. However, PLWH exhibited weaker CD4+ T cell responses to both HCoV-NL63 and SARS-CoV-2 than HIV-uninfected individuals. PLWH also had higher proportions of functionally exhausted (PD-1high) CD4+ T cells producing fewer proinflammatory cytokines (IFNγ and TNFα) and had elevated plasma IL-2 and IL-12(p70) levels compared to HIV-uninfected individuals. HIV status didn’t significantly affect IgG antibody levels against SARS-CoV-2 antigens or ACE2 binding inhibition activity.ConclusionOur results indicate that the decrease in SARS-CoV-2 specific T cell responses in PLWH may be attributable to reduced frequencies of pre-existing cross-reactive responses. However, HIV infection minimally affected the quality and magnitude of humoral responses, and this could explain why the risk of severe COVID-19 in PLWH is highly heterogeneous.

The role of human leukocyte antigen (HLA) class I and killer immunoglobulin-like receptor molecules in mediating acute retroviral syndrome (ARS) during human immunodeficiency virus type 1 (HIV-1) infection is unclear. Among 72 sub-Saharan African adults, HLA-A*23 was associated with lower odds of ARS (adjusted odds ratio, 0.10 [95% confidence interval, .01-.48]; P = .009), which warrants further studies to explore its role on HIV-1-specific immunopathogenesis.